A Brief Introduction to SFC-MS

Before SFC was coupled to mass spectrometers, systems used both UV and flame ionization detectors (FID).  The most prevalent SFC-MS sources are the atmospheric pressure ionization (API) sources, used in tandem with packed columns. Most of the columns commonly used for normal phase chromatography, both chiral and achiral, can be used with SFC  and integrating SFC and a mass analyzer is fairly straightforward and  easier than LC-MS, as CO2 is highly volatile, making it easier to convert effluents to the gas phase during the ionization process.

The most popular ionization sources for SFC-MS are atmospheric pressure chemical ionization (APCI) and electrospray ionization (ESI) as they allow direct infusion of the chromatographic effluents into a mass analyzer. Both ESI and APCI are used in the pharmaceutical industry, with ESI being more prevalent for LC-MS applications.

Atmospheric Pressure Chemical Ionization (APCI)

The APCI is the most common source currently used in SFC-MS. It is easily adaptable to SFC systems and can handle the high flow rates of a typical SFC method.  Since it is coupled with a highly volatile mobile phase, it does not suffer from reduced ionization efficiency as may be experienced in LC-MS at higher flow rates.

Source and Mass Analyzer Interfaces

The ionization source is only a part of the set-up in an SFC-MS system. How the sources are coupled to the mass analysers is also important. There are several options, some of which are more universal or user friendly and others that are more sensitive. This is more straightforward in LC-MS, whereas the phase behaviour of the CO2 makes these interfaces more challenging.  It is therefore necessary for the interface that links the ionization source to the mass spectrometer to control or counteract these problems.

Mass analyzers

Similar to LC-MS, the choice of mass analyzer depends on the application.

The workhorse mass analyzer for SFC-MS in the pharmaceutical industry is the single quadrupole mass spectrometer.                                                  

Practical Improvements in SFC-MS for Achiral Purification

For detailed information please see the following report on Practical Improvements SFC-MS for Achiral Purification.

Traditionally, SFC-UV and to a certain extent SFC-MS has suffered from a lack of sensitivity. Many new advancements in the past few years have increased the sensitivity and stabilized the baseline in SFCMS and overall, the future applications of SFC-MS look bright.